Hydrochloric Acid → Bumetanide Impurity 118

HRID 839057Notes

Reaction equation

HRID 839057 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH:7]1[C:12]([OH:13])=[CH:11][CH:10]=[C:9]([CH3:14])[CH:8]=1.Cl[C:16]1[C:21]([N+:22]([O-:24])=[O:23])=[CH:20][C:19]([C:25]([OH:27])=[O:26])=[CH:18][C:17]=1[S:28]([NH2:31])(=[O:30])=[O:29].Cl>O>[N+:22]([C:21]1[CH:20]=[C:19]([CH:18]=[C:17]([S:28](=[O:30])(=[O:29])[NH2:31])[C:16]=1[O:13][C:12]1[CH:7]=[CH:8][C:9]([CH3:14])=[CH:10][CH:11]=1)[C:25]([OH:27])=[O:26])([O-:24])=[O:23]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2879P-CresolHCID 11430Potassium CarbonateHCID 898934-Chloro-3-nitro-5-sulphamoylbenzoic acid

Product 1

HCID 21312073Bumetanide Impurity 118

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

124 g (0.9 mol) of potassium carbonate are dissolved in 800 ml of water. To this solution, there are added portionwise 1.6 mols of p-cresol and subsequently 112 g (0.4 mol) of 2-chloro-3-nitro-5-carboxy-benzenesulphonamide and the solution is heated to 85° C. The whole is stirred for 16 hours at this temperature, cooled to 25°-30° C and acidified with concentrated hydrochloric acid to pH 1. The oil which thereupon separates is isolated from the aqueous phase and subjected to steam distillation. Alternatively, it is also possible to adjust a pH-value of 8-9, to extract the excess phenol with ethyl acetate and then to acidify the aqueous phase. After having separated in this manner the excess p-cresol, the product crystallises upon cooling. By recrystallisation from acetone/H2O, the 3-nitro-4-(4'-methylphenoxy)-5-sulphamoylbenzoic acid melting at 236° C is obtained.

Workup

  1. temperaturecooled to 25°-30° C
  2. customThe oil which thereupon separates is isolated from the aqueous phase
  3. distillationsubjected to steam distillation
  4. extractionto extract the excess phenol with ethyl acetate
  5. customAfter having separated in this manner the excess p-cresol
  6. customthe product crystallises
  7. temperatureupon cooling
  8. customBy recrystallisation from acetone/H2O

Sources & evidence

ORD record
ord-c6ce7768046445038c40d4295a850cfd
Source dataset
uspto-grants-1978_06
Patent number
US04093735

Reaction notes

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